Rescue of glucocorticoid-programmed adipocyte inflammation by omega-3 fatty acid supplementation in the rat
Open accessAbstract
BACKGROUND: Adverse fetal environments predispose offspring to pathologies associated with the metabolic syndrome. Previously we demonstrated that adult offspring of dexamethasone-treated mothers had elevated plasma insulin and pro-inflammatory cytokines, effects prevented by a postnatal diet enriched with omega (n)-3 fatty acids. Here we tested whether prenatal glucocorticoid excess also programmed the adipose tissue phenotype, and whether this outcome is rescued by dietary n-3 fatty acids. METHODS: Offspring of control and dexamethasone-treated mothers (0.75 μg/ml in drinking water, day 13 to term) were cross-fostered to mothers on a standard (Std) or high n-3 (Hn3) diet at birth. Offspring remained on these diets post-weaning, and serum and retroperitoneal fat were obtained at 6 months of age (n = 5-8 per group). Serum was analysed for blood lipids and fatty acid profiles, adipocyte cross sectional area was measured by unbiased stereological analysis and adipose expression of markers of inflammation, glucocorticoid sensitivity and lipid metabolism were determined by RT-qPCR analysis. RESULTS: Serum total fatty acid levels were elevated (P < 0.01) in male offspring of dexamethasone-treated mothers, an effect prevented by Hn3 consumption. Prenatal dexamethasone also programmed increased adipose expression of Il6, Il1b (both P < 0.05) and Tnfa (P < 0.001) mRNAs regardless of fetal sex, but again this effect was prevented (for Il6 and Il1b) by Hn3 consumption. Offspring of dexamethasone-treated mothers had increased adipose expression of Gr (P = 0.008) and Ppara (P < 0.05) regardless of sex or postnatal diet, while 11bHsd1 was upregulated in males only. The Hn3 diet increased Ppard expression and reduced adipocyte size in all offspring (both P < 0.05) irrespective of prenatal treatment. CONCLUSIONS: Prenatal glucocorticoid exposure programmed increased expression of inflammatory markers and enhanced glucocorticoid sensitivity of adipose tissue. Partial prevention of this phenotype by high n-3 consumption indicates that postnatal dietary manipulations can limit adverse fetal programming effects on adipose tissue.
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Excess glucocorticoid exposure in utero is coupled with alterations in adipocyte morphology, expression of lipogenic genes, insulin signaling proteins, and inflammatory cytokine expression in the offspring WAT.
“This was coupled with alterations in adipocyte morphology, expression of lipogenic genes, insulin signaling proteins and inflammatory cytokine expression in the offspring WAT [124].”
From Developmental programming of offspring adipose tissue biology and obesity risk (2021) · cites this paper as [124]
The Results (no page listed) report increased adipose inflammatory-cytokine mRNAs and Ppara expression after prenatal dexamethasone exposure. They do not establish altered expression of lipogenic genes or insulin-signaling proteins. The Results section on adipocyte size attributes its reduction to the postnatal omega-3 diet, irrespective of prenatal treatment, rather than to glucocorticoid exposure. (LLM, conf=0.87)
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- Authors
- Mark, P. J., Wyrwoll, C. S., Zulkafli, I. S., Mori, T. A., & Waddell, B. J.
- Affiliations
- The University of Western Australia (AU)
- Corresponding author
- Mark, Peter J
- Venue
- Reproductive Biology and Endocrinology
- Published
- 2014
- Volume
- 12
- Issue
- 1
- Pages
- 39
- ISSN
- 1477-7827 (ISSN-L)
- PMC
- PMC4022445
- OpenAlex
- W2170686665
- Cited by
- 19
- References
- 49
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 2 · 2021: 3 · 2020: 4 · 2019: 2 · 2017: 2 · 2016: 1
- FWCI
- 0.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Reproductive Biology and Endocrinology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- UWA Profiles and Research Repository (UWA) (publishedVersion, other-oa)
- PubMed (publishedVersion)
- Funders
- Medical Research Council
- National Health and Medical Research Council
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- prenatal glucocorticoid exposure, dexamethasone, omega-3 fatty acids, adipocyte inflammation, adipose tissue, fetal programming, metabolic syndrome, cross-fostering, inflammatory cytokines, glucocorticoid receptor, PPARα, PPARδ, 11β-hydroxysteroid dehydrogenase type 1, adipocyte size, postnatal diet
- MeSH terms
- Animals, Dexamethasone, Disease Models, Animal, Female, Lactation, Male, Pregnancy, Pregnancy Complications, Random Allocation, Receptors, Glucocorticoid, Stress, Psychological, Weaning, Fatty Acids, Omega-3, Up-Regulation, Rats, Wistar, Inflammation Mediators, Dietary Supplements, Metabolic Syndrome, Maternal Nutritional Physiological Phenomena, 11-beta-Hydroxysteroid Dehydrogenase Type 1, Fetal Development, Intra-Abdominal Fat
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